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Biomedical subjects

J A Zubimendi

Publications and source records attributed to J A Zubimendi.

At least 19 recordsLinked to original sources
PubMed2005

Change in serum creatinine levels between 6 and 12 months and kidney graft survival: influence of proteinuria.

Renal function within the first year after transplantation has been shown to be an important parameter influencing long-term survival. In this study, we examined the relationship between long-term outcome in 365 renal transplants and renal function in the first year, expressed as serum creatinine (SCr) level at 6 months and at 1 year as well as namely deltaCr, the change in SCr between 6 months and 1 year. In addition, we examined the influence of the presence of proteinuria as a predictive factor for a worse evolution. Graft survival was worse among patients with higher deltaCr, especially among those who developed proteinuria. In a Cox regression analysis of long-term graft survival, both deltaCr and proteinuria were important predictors of half-life. The risk of graft loss when deltaCr >0.3 was 2.65 (1.8-3.8; P < .000), whereas the risk increased to 5.67 (3.3-9.4; P < .00) when proteinuria was present. In conclusion, deltaCr values predict long-term graft survival. Patients who developed proteinuria were at higher risk for graft loss compared with those without proteinuria. By using a combination of SCr and deltaCr with proteinuria, it is possible to identify a subset of transplant recipients with a predictably shortened half-life.

Adult↗
PubMed2005

Similar impact of slow and delayed graft function on renal allograft outcome and function.

Kidney transplant patients can be divided into three groups, according to the initial graft function. First-week dialyzed patients form the delayed graft function (DGF) group. Nondialyzed patients are divided into slow graft function (SGF) or immediate graft function (IGF) according to whether the day 5 serum creatinine was higher versus lower than 3 mg/dL, respectively. SGF patients showed worse graft survival, above higher incidence of acute rejection and lower renal function than IGF patients, although few reports have analyzed outcomes in these groups. We analyzed the impact of SGF on graft survival, first-year renal function, and incidence of acute rejection in 291 renal transplant patients. Creatinine was significantly worse at 12 months for SGF and DGF than for IGF patients (1.9 +/- 0.8 mg/dL, 1.8 +/- 0.7 mg/dL, 1.5 +/- 0.5 mg/dL, respectively; P < .05). There was no difference in first-year renal function between SGF and DGF. The acute rejection rate was higher among the SGF than the IGF group (45% vs 21%, P < .05), but not different from DGF patients (42%, P < .05). Graft survival was better among IGF than SGF or DGF patients, with no significant difference between the last two groups (3-year graft survival, 82%, 71%, 70%, respectively; log-rank test, P < .05). Kidney transplant recipients who develop SGF have a worse outcome than patients with IGF, similar to DGF patients. SGF patients show worse graft survival, worse renal function, and higher acute rejection rates than IGF patients, despite not needing dialysis.

Adult↗
PubMed2005

High initial blood levels of tacrolimus in overweight renal transplant recipients.

For the purpose of both efficacy and safety, exposure to tacrolimus and other immunosuppressive drugs must be monitored, since initial levels influence the development of acute rejection episodes, nephrotoxicity, and posttransplantation diabetes mellitus. The aim of this study was to identify risk factors for developing high initial tacrolimus blood levels. We analyzed clinical and biochemical parameters of 85 renal transplant recipients receiving tacrolimus-based immunosuppressive therapy by stratifying into subgroups of patients who displayed first tacrolimus concentrations higher and lower than 15 ng/mL. Patients with a first level of tacrolimus higher than 15 ng/mL were older (52 +/- 13 vs 40 +/- 12 years, P < .05) and had a larger body mass index (27 +/- 4 vs 23 +/- 3 kg/m2, P < .05) than patients with lower levels, despite receiving a lower weight-adjusted cumulative steroid dose (8.2 +/- 2.2 vs 9.3 +/- 2.5 mg/kg, P < .05). Upon logistic regression, age (RR 1.047, 95% CI 1.007 to 1.08, P = .021) and body mass index (RR 1.176, 95% CI 1.009 to 1.371, P = .036) remained significant risk factors for high initial blood levels of tacrolimus. As these subgroups of patients are most prone to develop posttransplantation glycemic disorders, attention must be paid to avoid high tacrolimus blood levels by diminishing initial tacrolimus doses or estimating them from ideal body weight.

Area Under Curve↗
PubMed2004

The macrophage infiltration index and matrix metalloproteinase-II expression as a predictor of chronic allograft rejection.

The presence of macrophages on renal biopsy specimens is considered an important cofactor in the development of chronic allograft nephropathy (CAN). Macrophages can activate the expression of matrix metalloproteinases (MMP), which induce glomerulosclerosis, arteriosclerosis, and interstitial fibrosis. The aim of our study was to demonstrate if they were related to the development of CAN. We analyzed matrix metalloproteinase (MMP) expression with specific monoclonal antibodies on 53 kidney biopsies performed due to the suspicion of a first acute rejection (AR) episode: 24 of the grafts have been lost due to CAN and the rest are still functioning. The group with CAN showed worse graft function and greater proteinuria from the beginning. The macrophage infiltration index (MI) expression was significantly higher in that group also (18.8 +/- 12 vs 12.5 +/- 9.15; P < .05), with a more important presence of macrophages in the interstitium and tubules. We observed a positive correlation between MI and tubular infiltration (r(2) = 0.52; P < .001) and between MMP-II and MI in the interstitium (r(2) = 0.3; P < .05) and with the global MI (r(2) = 0.3; P < 0.05). The last correlation was more powerful in the group with CAN (r(2) = 0.4; P < .05). According to our experience, global MI and tubular infiltration during an AR episode are good markers of long-term graft survival. The correlation between MI and MMP-II supports the role of macrophages in the development of CAN, although further studies are needed to clarify the nature of this relationship.

Biomarkers↗
PubMed2003

Effect of early graft function on patient survival in renal transplantation.

The influence of early graft function on long-term graft survival has been widely reported but its association with patient survival has received less attention. We investigated the effect of early renal function on patient survival and on cardiovascular disease after renal transplantation among 532 transplant patients who had grafts functioning for >1 year. Patients were classified into two groups, depending on the early creatinine clearance (< or >60 mL/min). We analyzed graft and patient survival, posttransplant cardiovascular disease, and the principal causes of death. Five- and 10-year graft and patient survival were lower among the group with worse early renal function. The main cause of death was vascular disease. Poorer early renal function increased the risk (RR) of patient death by 2.2-fold, and also the presence of posttransplant cardiovascular disease. In conclusion, patients with poor levels of early graft function are at an increased risk of death. These high-risk groups should be targeted for interventional studies to improve patient survival.

Creatinine↗
PubMed2003

Assessment of glomerular filtration rate in transplant recipients with severe renal insufficiency by Nankivell, Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault equations.

Measurement of glomerular filtration rate (GFR) is time consuming and cumbersome. Several formulas have been developed to predict creatinine clearance (CrCl) or GFR using serum creatinine (Cr) concentrations and demographic characteristics. However, few studies have been performed to discern the best formula to estimate GFR in kidney transplantation. In this study, Cockroft-Gault (CG), Nankivell, and Levey (MDRD) formulas were tested to predict GFR in 125 cadaveric renal transplant patients with severe renal insufficiency (GFR less than 30 mL/min per 1.73 m2). The GFR was estimated as the average Cr and urea clearances. The mean GFR estimated by averaged Cr and urea clearances (22.18+/-5.23 mL/min per 1.73 m2) was significantly different from the mean values yielded by the MDRD formula (20.42+/-6.65 mL/min per 1.73 m2, P=.000), the Nankivell formula (30.14+/-11.98 mL/min per 1.73 m2, P=.000), and the CG formula (29.42+/-8.64 mL/min per 1.73 m2, P=.000). The MDRD formula showed a better correlation (R=0.741, P=.000) than the CG (R=0.698, P=.000) and the Nankivell formulas (R=0.685, P=.000). Analysis of differences using the Bland-Altmann method demonstrated that MDRD gave the lowest bias (MDRD: -1.65+/-4.4 mL/min per 1.73 m2; CG: 7.33+/-6.24 mL/min per 1.73 m2; Nankivell: 8.05+/-9.23 mL/min per 1.73 m2) and narrower limits of agreement (Nankivell: -10.41-26.51 mL/min per 1.73 m2; CG: -5.15-19.81 mL/min per 1.73 m2; MDRD: -10.61-7.31 mL/min per 1.73 m2). In transplant patients with severe renal insufficiency, the MDRD equation seems better than the other formulas to estimate GFR.

Creatinine↗
PubMed2001

Hypertension and long-term renal allograft survival: effect of early glomerular filtration rate.

BACKGROUND: For many years, hypertension has been related to long-term survival of patients and kidney grafts, although the nature of this relationship has not been completely defined. The aim of this study was to analyse the influence of early glomerular filtration rate on post-transplant hypertension and on graft survival. METHODS: A total of 432 kidney transplanted patients on cyclosporin therapy, with a functioning graft for at least 1 year, were studied. They were divided into two groups depending on their early creatinine clearance: group A [<60 ml/min (n=270)] and group B [>60 ml/min (n=162)]. RESULTS: There were no differences in sex, aetiology of renal failure, number of retransplants, PRA, HLA mismatches and pre-transplant blood pressure. One year after transplantation, blood pressure was higher in group A (systolic BP 148/diastolic BP 86/mean BP 117) than in group B (systolic BP 140/diastolic BP 82/mean BP 111) (P<0.003). We observed a negative correlation between early creatinine clearance and 1-year blood pressure (P<0.01). Five and 10 year graft survival was 60 and 37% in group A and 87 and 69% in group B, respectively (P<0.000). A multivariate Cox analysis showed that 1-year blood pressure (P<0.0029, RR=1.76) and early creatinine clearance (P<0.000, RR=3.27) had a significant influence on graft survival. CONCLUSIONS: The 1-year post-transplant blood pressure is a non-immunological risk factor in long-term graft survival. Patients with a lower initial glomerular filtration rate are more susceptible to the development of secondary hypertension and worse graft survival.

Adult↗
PubMed2000

Circulating levels of matrix metalloproteinases MMP-3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy.

BACKGROUND: Chronic transplant nephropathy remains the major cause of graft loss after the first year post transplant, with the exception of death with functioning graft. The histological hallmark of chronic kidney rejection is progressive fibrosis in which extracellular matrix turnover plays an important role. This turnover is regulated by several systems of connective tissue proteases, the matrix metalloproteinases family being one of them. Every metalloproteinase exerts a different function over extracellular matrix proteins and can contribute to the pathogenesis of several diseases, such as rheumatoid arthritis and glomerulonephritis. The role of metalloproteinases in the pathogenesis of chronic transplant nephropathy and in kidney transplantation has not yet been addressed. METHODS: We measured the serum levels of proMMP-1, proMMP-2 and proMMP-3 by ELISA in 40 patients with chronic transplant nephropathy, 30 with acute rejection, 30 with stable graft function for a time equivalent to chronic transplant nephropathy, 30 with stable graft function for a time equivalent to acute rejection, and 30 healthy age-paired blood donors. RESULTS: Serum proMMP-2 and proMMP-3 were significantly higher in patients with chronic transplant nephropathy than in patients with acute rejection, stable graft function and healthy donors. The most striking finding was the significant positive correlation observed between serum levels of proMMP-3 and serum creatinine, and between circulating levels of proMMP-2 and proteinuria. Serum concentration of proMMP-1 was increased in patients with acute rejection compared with those with stable graft function and healthy donors. CONCLUSIONS: Serum proMMP-2 and proMMP-3 reflect the changes of glomerular and interstitial extracellular matrix in chronic transplant nephropathy, suggesting that they could play a role in the pathogenesis of this condition. Acute rejection is associated with increased levels of proMMP-1, which could be a reflection of the stimulation induced by a number of inflammatory cytokines produced in such a process.

Acute Disease↗